INVOLVEMENT OF ENDOGENOUS NITRIC-OXIDE IN THE INHIBITION BY ENDOTOXINAND INTERLEUKIN-1-BETA OF GASTRIC-ACID SECRETION

Administration of Escherichia coli endotoxin abolished the acid secret ory response induced by a bolus injection of pentagastrin in the conti nuously perfused stomach of the anaesthetized rat. Likewise, acid secr etion stimulated by the continuous intravenous perfusion of pentagastr in was inhibited by administration of interleukin-1 beta (IL-1 beta). In both cases pretreatment with N-G-nitro-L-arginine methyl ester (L-N AME) but not dexamethasone or indomethacin substantially restored the secretory responses to pentagastrin. The actions of L-NAME were revers ed by the prior administration of L-arginine but not by its enantiomer D-arginine. Even though L-NAME increased blood pressure, this does no t seem to be the mechanism by which endotoxin-induced acid inhibition was prevented, since similar systemic presser responses induced by phe nylephrine had no such effect. The secretory response elicited by pent agastrin in the isolated lumen perfused stomach of the rat was not inf luenced by incubation (100 min) with IL-1 beta. These observations sug gest that the acute inhibition of acid responses to pentagastrin by en dotoxin and IL-1 beta involves nitric oxide (NO) synthesis from L-argi nine.